Nager syndrome

Nager syndrome, also known as Nager acrofacial dysostosis or preaxial acrofacial dysostosis, is a rare genetic disorder characterized by the combination of mandibulofacial dysostosis (underdevelopment of the facial bones) and preaxial limb defects (abnormalities primarily affecting the thumb side of the upper limbs). It belongs to a group of conditions called acrofacial dysostoses, which involve simultaneous craniofacial and limb malformations. The craniofacial features of Nager syndrome closely resemble those seen in Treacher Collins syndrome and include downslanting palpebral fissures, malar (cheekbone) hypoplasia, micrognathia (small lower jaw), and external ear malformations. Cleft palate or absent soft palate is common. Conductive hearing loss frequently occurs due to malformation of the middle ear structures. The limb abnormalities predominantly affect the upper extremities and include hypoplasia or absence of the thumbs, hypoplasia or absence of the radius, and radioulnar synostosis (fusion of the forearm bones). The lower limbs are less commonly affected but may show mild abnormalities. Nager syndrome is caused by pathogenic variants in the SF3B4 gene, which encodes a component of the spliceosome involved in pre-mRNA processing. The condition is inherited in an autosomal dominant pattern, though many cases arise from de novo (new) mutations. Airway management is often a critical concern in the neonatal period due to severe micrognathia, and some infants may require tracheostomy. Treatment is multidisciplinary and symptomatic, involving craniofacial surgery, orthopedic interventions for limb anomalies, hearing aids or auditory rehabilitation, speech therapy, and feeding support. Mandibular distraction osteogenesis may be employed to address airway obstruction. With appropriate management, intellectual development is typically normal.

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